ANTI-IL-4 TREATMENT OF SCHISTOSOMA-MANSONI-INFECTED MICE INHIBITS DEVELOPMENT OF T-CELLS AND NON-B, NON-T CELLS EXPRESSING TH2 CYTOKINES WHILE DECREASING EGG-INDUCED HEPATIC-FIBROSIS

Increasing evidence suggests that schistosome egg granulomas are prima rily Th2 cellular reactions. Mice infected with Schistosoma mansoni we re treated with a neutralizing mAb against IL-4 to evaluate the role o f this cytokine in the generation of parasite egg-induced cell-mediate d responses and hepatic pathology. Animals treated with anti-IL-4 befo re egg deposition showed decreased IL-4, IL-5, and IL-10 production in response to in vitro antigenic stimulations and decreased IL-5 and IL -13 mRNA levels in the liver. As observed previously, non-B, non-T cel ls were a major source of IL-4 in infected mice treated with control m Ab, and the diminished IL-4 response in anti-IL-4-treated animals was shown to be caused at least in part by a reduction in the number of th ese cells, as well as by decreased secretion of IL-4 per cell. In cont rast, production of the Th1 cytokines IL-2 and IFN-gamma was elevated in anti-IL-4-treated infected mice in vitro, and the corresponding mRN As in the liver were increased. Anti-IL-4 treatment did not consistent ly reduce the size of hepatic granulomas around S. mansoni eggs, but m arkedly inhibited granuloma formation in the lungs of the same animals after i.v. egg injection. Nevertheless, anti-IL-4-treated infected mi ce showed consistent and marked reductions in hepatic collagen deposit ion. These findings indicate that IL-4 plays a major role in the devel opment of the Th2 response in S. mansoni-infected mice and contributes to the pathogenesis of hepatic fibrosis.